During the last several decades, the diversification of economic activities has become a paramount policy for nations and cities with heavy dependence on a single economic driver. Particularly island economies, relying mainly on tourism income, are among the most vulnerable ones to the shocks of global financial crises. In the recent years, some of these tourist islands had attempts to diversify their economic activities by moving towards a knowledge and innovation economy. This paper places one of these islands—Florianópolis, the capital city of the Brazilian state of Santa Catarina—under the microscope to address the question of ‘what it takes to transform a tourist island into an innovation capital’. In order to tackle this question, the study examines economic, social, spatial, and governance conditions and performances, along with the plans and processes of Florianópolis in moving towards an internationally recognized smart innovation island. The methodologic approach includes systematic review of the literature and qualitative analysis of the key development domains of Florianópolis through the lens of knowledge-based urban development. The results of this study provide insights into how to transform a resource-based economy into a knowledge-based one—by disclosing the transition journey of Florianópolis, including progress, challenges, and the new path creation processes. The findings are particularly useful for tourist islands that are aiming for an aspiring knowledge-based urban development and smart city transformation.